Targeted regulation of adipose tissue macrophages from an immunometabolic perspective: a novel therapeutic approach for obesity-related metabolic disorders

The global prevalence of obesity and its associated metabolic syndromes, characterized by chronic inflammation and metabolic disorders, poses a major health threat worldwide. This makes it urgent to gain a deeper understanding of its pathogenesis and to develop new therapeutic strategies. Adipose tissue macrophages (ATMs), as central regulators of the adipose tissue immune microenvironment, exhibit functional polarization closely linked to obesity-associated chronic low-grade inflammation and insulin resistance. This review systematically elucidates the mechanisms of metabolic reprogramming in adipose tissue microenvironment under obesity, focusing on how profound alterations in their glucose, lipid, and amino acid metabolic networks drive their shift toward a pro-inflammatory phenotype. Building on this, we review the mechanisms of action and latest research advances in emerging therapeutic strategies, including mitochondrial-targeted interventions, extracellular vesicle (EV)-mediated molecular delivery, probiotic/prebiotic modulation, probiotic extracellular vesicles, and nanotechnology-enabled precision interventions. Finally, this review outlines the challenges and future directions for treating obesity-related diseases by precisely regulating the EV-ATMs metabolic axis.